Descrizione del progetto
Sequenziamento in situ per mappare le interazioni cellulari nella mucosa intestinale
In condizioni fisiologiche, l’epitelio intestinale costituisce una barriera fisica dinamica che funge da prima linea di difesa immunitaria. Un danno al monostrato di cellule epiteliali intestinali specializzate induce l’interruzione dell’omeostasi immunitaria intestinale e porta a malattie infiammatorie intestinali, quali la colite ulcerosa e il morbo di Crohn. Considerata la crescente incidenza di malattie infiammatorie intestinali nelle società moderne, gli scienziati del progetto GUTMAPS, finanziato dall’UE, mirano a studiare il tessuto intestinale con una risoluzione senza precedenti. Per fare ciò, eseguiranno il sequenziamento in situ per profilare singole cellule, mapperanno le interazioni cellula-cellula e contribuiranno a creare una migliore comprensione di questo organo in condizioni di salute e di malattia.
Obiettivo
The intestinal epithelium is the first line of defence of the mucosal immune system because it acts as a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. This barrier is mainly formed by a monolayer of specialised intestinal epithelial cells (IECs) that are crucial in maintaining intestinal homeostasis. Damage to this epithelial layer can increase intestinal permeability and lead to abnormalities in interactions between IECs, stromal cells and immune cells in the underlying lamina propria thereby disturbing the intestinal immune homeostasis, all of which are a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major forms of IBD, affecting an estimated 4 million people in the United States and Europe and have a rising incidence in the developing world. Recent single cell RNA seq (scRNAseq) studies of the intestine have allowed us to understand this organ in unprecedented detail, however, such studies still require the dissociation of tissue and loss of spatial resolution. With this project, I would like to take advantage of recent advances in in-situ sequencing to study intestinal tissue in toto and by combining this with the available scRNA-seq data, generate spatial maps of the intestine (GUTMAPS). The results obtained here will allow us to look at tissue composition and cell-cell interactions with unprecedented resolution in normal and diseased mucosa.
Campo scientifico
- natural sciencesearth and related environmental sciencesphysical geographycartography
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesbasic medicinephysiologyhomeostasis
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
3015 GD Rotterdam
Paesi Bassi